The Nursing Activities Score Per Nurse Ratio Is Associated With In-Hospital Mortality, Whereas the Patients Per Nurse Ratio Is Not.

OBJECTIVES: Studies have shown contradicting results on the association of nursing workload and mortality. Most of these studies expressed workload as patients per nurse ratios; however, this does not take into account that some patients require more nursing time than others. Nursing time can be quantified by tools like the Nursing Activities Score. We investigated the association of the Nursing Activities Score per nurse ratio, respectively, the patients per nurse ratio with in-hospital mortality in ICUs. DESIGN: Retrospective analysis of the National Intensive Care Evaluation database. SETTING: Fifteen Dutch ICUs. PATIENTS: All ICU patients admitted to and registered ICU nurses working at 15 Dutch ICUs between January 1, 2016, and January 1, 2018, were included. The association of mean or day 1 patients per nurse ratio and Nursing Activities Score per nurse ratio with in-hospital mortality was analyzed using logistic regression models. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nursing Activities Score per nurse ratio greater than 41 for both mean Nursing Activities Score per nurse ratio as well as Nursing Activities Score per nurse ratio on day 1 were associated with a higher in-hospital mortality (odds ratios, 1.19 and 1.17, respectively). After case-mix adjustment the association between a Nursing Activities Score per nurse ratio greater than 61 for both mean Nursing Activities Score per nurse ratio as well as Nursing Activities Score per nurse ratio on day 1 and in-hospital mortality remained significant (odds ratios, 1.29 and 1.26, respectively). Patients per nurse ratio was not associated with in-hospital mortality. CONCLUSIONS: A higher Nursing Activities Score per nurse ratio was associated with higher in-hospital mortality. In contrast, no association was found between patients per nurse ratios and in-hospital mortality in The Netherlands. Therefore, we conclude that it is more important to focus on the nursing workload that the patients generate rather than on the number of patients the nurse has to take care of in the ICU.

Early Prediction of Intensive Care Unit-Acquired Weakness: A Multicenter External Validation Study.

OBJECTIVES: An early diagnosis of intensive care unit-acquired weakness (ICU-AW) is often not possible due to impaired consciousness. To avoid a diagnostic delay, we previously developed a prediction model, based on single-center data from 212 patients (development cohort), to predict ICU-AW at 2 days after ICU admission. The objective of this study was to investigate the external validity of the original prediction model in a new, multicenter cohort and, if necessary, to update the model. METHODS: Newly admitted ICU patients who were mechanically ventilated at 48 hours after ICU admission were included. Predictors were prospectively recorded, and the outcome ICU-AW was defined by an average Medical Research Council score <4. In the validation cohort, consisting of 349 patients, we analyzed performance of the original prediction model by assessment of calibration and discrimination. Additionally, we updated the model in this validation cohort. Finally, we evaluated a new prediction model based on all patients of the development and validation cohort. RESULTS: Of 349 analyzed patients in the validation cohort, 190 (54%) developed ICU-AW. Both model calibration and discrimination of the original model were poor in the validation cohort. The area under the receiver operating characteristics curve (AUC-ROC) was 0.60 (95% confidence interval [CI]: 0.54-0.66). Model updating methods improved calibration but not discrimination. The new prediction model, based on all patients of the development and validation cohort (total of 536 patients) had a fair discrimination, AUC-ROC: 0.70 (95% CI: 0.66-0.75). CONCLUSIONS: The previously developed prediction model for ICU-AW showed poor performance in a new independent multicenter validation cohort. Model updating methods improved calibration but not discrimination. The newly derived prediction model showed fair discrimination. This indicates that early prediction of ICU-AW is still challenging and needs further attention.

Using Nursing Activities Score to Assess Nursing Workload on a Medium Care Unit.

BACKGROUND: The medium care unit (MCU) or "stepdown" unit is an increasingly important, but understudied care environment. With an aging population and more patients with complex multiple diseases, many patients often require a higher level of inpatient care even when full intensive care is not indicated. However, the nurse-to-patient ratio required on a MCU is neither well defined nor clear whether this ratio should be adjusted per shift. The Nursing Activities Score (NAS) is an effective instrument for measuring nursing workload in the intensive care unit (ICU) but has not been used in an MCU. The aim of this study was to measure the nursing workload per 8-hour shift on an MCU using the NAS and compare it with the NAS from an ICU in the same hospital. We also compared the NAS between groups of patients with different admission sources. METHODS: The NAS was prospectively measured per patient per shift for 2 months in a 9-bed tertiary referral university hospital MCU and during a similar period in an ICU in the same hospital. RESULTS: The mean NAS per patient did not differ between day (7:30 AM to 4:00 PM) and evening (3:00 PM to 11:30 PM) shifts, but the NAS was significantly lower during the night shift (11:00 PM to 8:00 AM) than during the day (P < 0.0001) and evening (P < 0.0001) shifts. The mean NASs in the ICU for day and night shifts were significantly lower than the scores in the MCU (P = 0.0056 and P < 0.0001, respectively), but NAS during the evening shift did not differ between the ICU and the MCU. The mean NAS for patients admitted to the MCU from the accident and emergency department was significantly higher than for those admitted from the ICU (P = 0.002), recovery (P = 0.002), and general ward (P < 0.0001). Patients on the MCU had a NAS comparable with that of ICU patients. CONCLUSIONS: In our university hospital, NAS was higher during the day and evening hours and lower at night. We also found that patients from accident and emergency had a higher NAS than those admitted to the MCU from other locations. NAS in the MCU was not lower than the NAS in the ICU. Because of its ability to discriminate between day and evening workloads and between patients from different sources, the NAS may assist MCU managers in assessing staffing needs.

Quality improvement of Dutch ICUs from 2009 to 2021: A registry based observational study.

PURPOSE: To investigate the development in quality of ICU care over time using the Dutch National Intensive Care Evaluation (NICE) registry. MATERIALS AND METHODS: We included data from all ICU admissions in the Netherlands from those ICUs that submitted complete data between 2009 and 2021 to the NICE registry. We determined median and interquartile range for eight quality indicators. To evaluate changes over time on the indicators, we performed multilevel regression analyses, once without and once with the COVID-19 years 2020 and 2021 included. Additionally we explored between-ICU heterogeneity by calculating intraclass correlation coefficients (ICC). RESULTS: 705,822 ICU admissions from 55 (65%) ICUs were included in the analyses. ICU length of stay (LOS), duration of mechanical ventilation (MV), readmissions, in-hospital mortality, hypoglycemia, and pressure ulcers decreased significantly between 2009 and 2019 (OR <1). After including the COVID-19 pandemic years, the significant change in MV duration, ICU LOS, and pressure ulcers disappeared. We found an ICC ≤0.07 on the quality indicators for all years, except for pressure ulcers with an ICC of 0.27 for 2009 to 2021. CONCLUSIONS: Quality of Dutch ICU care based on seven indicators significantly improved from 2009 to 2019 and between-ICU heterogeneity is medium to small, except for pressure ulcers. The COVID-19 pandemic disturbed the trend in quality improvement, but unaltered the between-ICU heterogeneity.

Comparison of Prognostic Accuracy of 3 Delirium Prediction Models.

BACKGROUND: Delirium is a severe complication in critical care patients. Accurate prediction could facilitate determination of which patients are at risk. In the past decade, several delirium prediction models have been developed. OBJECTIVES: To compare the prognostic accuracy of the PRE-DELIRIC, E-PRE-DELIRIC, and Lanzhou models, and to investigate the difference in prognostic accuracy of the PRE-DELIRIC model between patients receiving and patients not receiving mechanical ventilation. METHODS: This retrospective study involved adult patients admitted to the intensive care unit during a 2-year period. Delirium was assessed by using the Confusion Assessment Method for the Intensive Care Unit or any administered dose of haloperidol or quetiapine. Model discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUC); values were compared using the DeLong test. RESULTS: The study enrolled 1353 patients. The AUC values were calculated as 0.716 (95% CI, 0.688-0.745), 0.681 (95% CI, 0.650-0.712), and 0.660 (95% CI, 0.629-0.691) for the PRE-DELIRIC, E-PRE-DELIRIC, and Lanzhou models, respectively. The difference in model discrimination was statistically significant for comparison of the PRE-DELIRIC with the E-PRE-DELIRIC (AUC difference, 0.035; P = .02) and Lanzhou models (AUC difference, 0.056; P < .001). In the PRE-DELIRIC model, the AUC was 0.711 (95% CI, 0.680-0.743) for patients receiving mechanical ventilation and 0.664 (95% CI, 0.586-0.742) for those not receiving it (difference, 0.047; P = .27). CONCLUSION: Statistically significant differences in prognostic accuracy were found between delirium prediction models. The PRE-DELIRIC model was the best-performing model and can be used in patients receiving or not receiving mechanical ventilation.

Nurse Operation Workload (NOW), a new nursing workload model for intensive care units based on time measurements: An observational study.

BACKGROUND: Several instruments have been developed to measure nursing workload. The commonly used Nursing Activities Score (NAS) and Therapeutic Intervention Scoring System (TISS) are applied to all types of ICU patients. Former research showed that NAS explained 59 to 81% of actual nursing time, whereas the Therapeutic Intervention Scoring System (TISS) described only 43% of the actual nursing time. In both models the development was not based on time measurements. OBJECTIVES: The aim of this study was to develop a time-based model which can assess patient related nursing workload more accurately and to evaluate whether patient characteristics influence nursing time and therefore should be included in the model. DESIGN: Observational study design. SETTING: All 82 Dutch ICUs participate in the National Intensive Care Evaluation (NICE) quality registry. Fifteen of these ICUs are participating in the newly implemented voluntary nursing capacity module. Seven of these ICUs voluntarily participated in this study. PARTICIPANTS: The patient(s) that were under the responsibility of a chosen nurse were followed by the observer during the entire shift. METHODS: Time spent per nursing activity per patient was measured in different shifts in seven Dutch ICUs. Nursing activities were measured using an in-house developed web application. Three different models of varying complexity (1. nursing activities only; 2. nursing activities and case-mix correction; 3. complex model with case-mix correction per nursing activity) were developed to explain the total amount of nursing time per patient. The performance of the three models was assessed in 1000 bootstrap samples using the squared Pearson correlation coefficient (R2), Root Mean Squared Prediction Error (RMSPE), Mean Absolute Prediction Error (MAPE), and prediction bias. RESULTS: In total 287 unique patients have been observed in 371 shifts. Model one's Pearson's R was 0.89 (95%CI 0.86-0.92), model two with case-mix correction 0.90 (95%CI 0.88-0.93), and the third complex model 0.64 (95%CI 0.56-0.72) compared with the actual patient related nursing workload. CONCLUSION: The newly developed Nurse Operation Workload (NOW) model outperforms existing models in measuring nursing workload, while it includes a lower number of activities and therewith lowers the registration burden. Case-mix correction does not further improve the performance of this model. The patient related nursing workload measured by the NOW gives insight in the actual nursing time needed by patients and can therefore be used to evaluate the average workload per patient per nurse.

Association between organizational characteristics and adequate pain management at the intensive care unit.

PURPOSE: Half of the patients experience pain during their ICU stay which is known to influence their outcomes. Nurses and physicians encounter organizational barriers towards pain assessment and treatment. We aimed to evaluate the association between adequate pain management and nurse to patient ratio, bed occupancy rate, and fulltime presence of an intensivist. MATERIALS AND METHODS: We performed unadjusted and case-mix adjusted mixed-effect logistic regression modeling on data from thirteen Dutch ICUs to investigate the association between ICU organizational characteristics and adequate pain management, i.e. patient-shift observations in which patients' pain was measured and acceptable, or unacceptable and normalized within 1 h. All ICU patients admitted between December 2017 and June 2018 were included, excluding patients who were delirious, comatose or had a Glasgow coma score < 8 at the first day of ICU admission. RESULTS: Case-mix adjusted nurse to patient ratios of 0.70 to 0.80 and over 0.80 were significantly associated with adequate pain management (OR [95% confidence interval] of respectively 1.14 [1.07-1.21] and 1.16 [1.08-1.24]). Bed occupancy rate and intensivist presence showed no association. CONCLUSION: Higher nurse to patient ratios increase the percentage of patients with adequate pain management especially in medical and mechanically ventilated patients.

Workload scoring systems in the Intensive Care and their ability to quantify the need for nursing time: A systematic literature review.

INTRODUCTION: The Intensive Care Unit is a resource intense service with a high nursing workload per patient resulting in a low ratio of patients per nurse. This review aims to identify existing scoring systems for measuring nursing workload on the Intensive Care and assess their validity and reliability to quantify the needed nursing time. METHODS: We conducted a systematic review of the literature indexed before 01/Mar/2018 in the bibliographic databases MEDLINE, Embase, and Cinahl. Full-text articles were selected and data on systems measuring nursing workload on the Intensive Care and translation of this workload into the amount of nursing time needed was extracted. RESULTS: We included 71 articles identifying 34 different scoring systems of which 27 were included for further analysis as these described a translation of workload into nursing time needed. Almost all systems were developed with nurses. The validity of most scoring systems was evaluated by comparing them with another system (59%) or by using time measurements (26%). The most common way to translate workload-scores into nursing time needed was by categorizing the Nurse:Patient-ratios. Validation of the Nurse:Patient-ratios was mostly evaluated by comparing the results with other systems or with the actual planning and not with objective time measurements. CONCLUSION: Despite the large attention given to nursing workload systems for Intensive Care, only a few systems objectively evaluated the validity and reliability of measuring nursing workload with moderate results. The Nursing Activity Score system performed best. Poor methodology for the translation of workload scores into Nurse:Patient-ratio weakens the value of nursing workload scoring systems in daily Intensive Care practice.

Measuring quality indicators to improve pain management in critically ill patients.

PURPOSE: To evaluate the quality of pain assessment in Dutch ICUs and its room for improvement. MATERIALS AND METHODS: We used a modified RAND method to develop pain assessment indicators. We measured performance on the indicators using retrospectively collected pain measurement data from Dutch ICUs, which are all mixed medical - surgical, of three months within October 2016-May 2017. We assessed the room for improvement, feasibility of data collection, and reliability of the indicators. RESULTS: We defined four pain assessment indicators. We analyzed 45,688 patient-shift observations from 15 ICUs. In 69.2% (IQR 58.7-84.9) of the patient-shifts pain was measured at least once (indicator 1); in 56.7% (IQR 49.6-73.5) pain scores were acceptable (indicator 2); in 11.7% (IQR 5.6-26.4) pain measurements with unacceptable scores were repeated within 1 h (indicator 3); and in 10.9% (IQR 5.1-20.1) unacceptable scores normalized within 1 h (indicator 4). We found data collection feasible because data were available for >79.3% of the admissions, and all indicators reliable as they produced consistent performance scores. CONCLUSIONS: There is substantial variation in pain assessment across Dutch ICUs, and ample room for improvement. With this study we took a first step towards quality assurance of pain assessment in Dutch ICUs.

Impact of audit and feedback with action implementation toolbox on improving ICU pain management: cluster-randomised controlled trial.

BACKGROUND: Audit and feedback (A&F) enjoys widespread use, but often achieves only marginal improvements in care. Providing recipients of A&F with suggested actions to overcome barriers (action implementation toolbox) may increase effectiveness. OBJECTIVE: To assess the impact of adding an action implementation toolbox to an electronic A&F intervention targeting quality of pain management in intensive care units (ICUs). TRIAL DESIGN: Two-armed cluster-randomised controlled trial. Randomisation was computer generated, with allocation concealment by a researcher, unaffiliated with the study. Investigators were not blinded to the group assignment of an ICU. PARTICIPANTS: Twenty-one Dutch ICUs and patients eligible for pain measurement. INTERVENTIONS: Feedback-only versus feedback with action implementation toolbox. OUTCOME: Proportion of patient-shift observations where pain management was adequate; composed by two process (measuring pain at least once per patient in each shift; re-measuring unacceptable pain scores within 1 hour) and two outcome indicators (acceptable pain scores; unacceptable pain scores normalised within 1 hour). RESULTS: 21 ICUs (feedback-only n=11; feedback-with-toolbox n=10) with a total of 253 530 patient-shift observations were analysed. We found absolute improvement on adequate pain management in the feedback-with-toolbox group (14.8%; 95% CI 14.0% to 15.5%) and the feedback-only group (4.8%; 95% CI 4.2% to 5.5%). Improvement was limited to the two process indicators. The feedback-with-toolbox group achieved larger effects than the feedback-only group both on the composite adequate pain management (p<0.05) and on measuring pain each shift (p<0.001). No important adverse effects have occurred. CONCLUSION: Feedback with toolbox improved the number of shifts where patients received adequate pain management compared with feedback alone, but only in process and not outcome indicators. TRIAL REGISTRATION NUMBER: NCT02922101.

Effect of Bronchoscopy on Gas Exchange and Respiratory Mechanics in Critically Ill Patients With Atelectasis: An Observational Cohort Study.

Background: Atelectasis frequently develops in critically ill patients and may result in impaired gas exchange among other complications. The long-term effects of bronchoscopy on gas exchange and the effects on respiratory mechanics are largely unknown. Objective: To evaluate the effect of bronchoscopy on gas exchange and respiratory mechanics in intensive care unit (ICU) patients with atelectasis. Methods: A retrospective, single-center cohort study of patients with clinical indication for bronchoscopy because of atelectasis diagnosed on chest X-ray (CXR). Results: In total, 101 bronchoscopies were performed in 88 ICU patients. Bronchoscopy improved oxygenation (defined as an increase of PaO2/FiO2 ratio > 20 mmHg) and ventilation (defined as a decrease of > 2 mmHg in partial pressure of CO2 in arterial blood) in 76 and 59% of procedures, respectively, for at least 24 h. Patients with a low baseline value of PaO2/FiO2 ratio and a high baseline value of PaCO2 were most likely to benefit from bronchoscopy. In addition, in intubated and pressure control ventilated patients, respiratory mechanics improved after bronchoscopy for up to 24 h. Mild complications, and in particular desaturation between 80 and 90%, were reported in 13% of the patients. Conclusions: In selected critically ill patients with atelectasis, bronchoscopy improves oxygenation, ventilation, and respiratory mechanics for at least 24 h.

Epidemiology of acute lung injury and acute respiratory distress syndrome in The Netherlands: a survey.

BACKGROUND: The characteristics, incidence and risk factors for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) may depend on definitions and geography. METHODS: A prospective, 3-day point-prevalence study was performed by a survey of all intensive care units (ICU) in the Netherlands (n=96). Thirty-six ICU's responded (37%), reporting on 266 patients, of whom 151 were mechanically ventilated. The questionnaire included criteria and potential risk factors for ALI/ARDS, according to the North American-European Consensus Conference (NAECC) or the lung injury score (LIS>or=2.5). RESULTS: Agreement between definitions was fair (kappa 0.31-0.42, P=0.001). ALI/ARDS was characterized, regardless of definition, by radiographic densities, low oxygenation ratios, high inspiratory O(2) and airway pressure requirements. Depending on definitions, ALI and ARDS accounted for about 12-33% and 7-9% of ICU admissions per year, respectively, constituting 21-58% (ALI) and 13-16% (ARDS) of all mechanically ventilated patients. The annual incidences of ALI and ARDS are 29.3 (95%CI 18.4-40.1) and 24.0 (95%CI 14.2-33.8) by NAECC, respectively, and are, respectively, 83.6 (95%CI 65.3-101.9) and 20.9 (95%CI 11.7-30.1) by LIS per 100,000. Risk factors for ALI/ARDS were aspiration, pneumonia, sepsis and chronic alcohol abuse (the latter only by NAECC). CONCLUSION: The effect of definitions of ALI/ARDS on mechanical ventilation in the Netherlands is small. Nevertheless, the incidence of ALI/ARDS may be higher than in other European countries but lower than in the USA, and the incidence of ALI by LIS may overestimate compared to that by NAECC. Aspiration, pneumonia, sepsis and chronic alcohol abuse are major risk factors, largely independent of definitions.

Predicting a low cortisol response to adrenocorticotrophic hormone in the critically ill: a retrospective cohort study.

INTRODUCTION: Identification of risk factors for diminished cortisol response to adrenocorticotrophic hormone (ACTH) in the critically ill could facilitate recognition of relative adrenal insufficiency in these patients. Therefore, we studied predictors of a low cortisol response to ACTH. METHODS: A retrospective cohort study was conducted in a general intensive care unit of a university hospital over a three year period. The study included 405 critically ill patients, who underwent a 250 microg ACTH stimulation test because of prolonged hypotension or need for vasopressor/inotropic therapy. Plasma cortisol was measured before and 30 and 60 min after ACTH injection. A low adrenal response was defined as an increase in cortisol of less than 250 nmol/l or a peak cortisol level below 500 nmol/l. Various clinical variables were collected at admission and on the test day. RESULTS: A low ACTH response occurred in 63% of patients. Predictors, in multivariate analysis, included sepsis at admission, low platelets, low pH and bicarbonate, low albumin levels, high Sequential Organ Failure Assessment score and absence of prior cardiac surgery, and these predictors were independent of baseline cortisol and intubation with etomidate. Baseline cortisol/albumin ratios, as an index of free cortisol, were directly related and increases in cortisol/albumin were inversely related to disease severity indicators such as the Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score (Spearman r = -0.21; P < 0.0001). CONCLUSION: In critically ill patients, low pH/bicarbonate and platelet count, greater severity of disease and organ failure are predictors of a low adrenocortical response to ACTH, independent of baseline cortisol values and cortisol binding capacity in blood. These findings may help to delineate relative adrenal insufficiency and suggest that adrenocortical suppression occurs as a result of metabolic acidosis and coagulation disturbances.

Development of a Web-Based Quality Dashboard Including a Toolbox to Improve Pain Management in Dutch Intensive Care.

Audit and feedback (A&F) is a common strategy to improve quality of care. Meta-analyses have indicated that A&F may be more effective in realizing desired change when baseline performance is low, it is delivered by a supervisor or colleague, it is provided frequently and in a timely manner, it is delivered in both verbal and written formats, and it includes specific targets and an action plan. However, there is little information to guide operationalization of these factors. Researchers have consequently called for A&F interventions featuring well-described and carefully justified components, with their theoretical rationale made explicit. This paper describes the rationale and development of a quality dashboard including an improvement toolbox for four previous developed pain indicators, guided by Control Theory.

Percutaneous dilatational tracheostomy in the ICU: optimal organization, low complication rates, and description of a new complication.

STUDY OBJECTIVES: To assess short-term and long-term complications of bronchoscopy-guided, percutaneous dilatational tracheostomy (PDT) and surgical tracheostomy (ST) and to report a complication of PDT that has not been described previously. DESIGN: Prospective survey. SETTING: University teaching hospital. PATIENTS: Two hundred eleven critically ill patients in our ICU. INTERVENTIONS: PDT was performed in 174 patients, under bronchoscopic guidance in most cases. ST was performed in 40 patients. RESULTS: No procedure-related fatalities occurred during PDT or ST. The incidence of significant complications (eg, procedure-related transfusion of fresh-frozen plasma, RBCs, or platelets, malpositioning or kinking of the tracheal cannula, deterioration of respiratory parameters lasting for > 36 h following the procedure, or stomal infection) in patients undergoing PDT was 4.0% overall and 3.0% when bronchoscopic guidance was used. No cases of paratracheal insertion, pneumothorax, pneumomediastinum, tracheal laceration, or clinically significant tracheal stenosis occurred in patients undergoing PDT. We attribute this low rate of complications to procedural and organizational factors such as bronchoscopic guidance, performance by or supervision of all PDTs by physicians with extensive experience in this procedure, and airway management by physicians who were well-versed in (difficult) airway management. In addition, an ear-nose-throat surgeon participated in the procedure in case conversion of the procedure to an ST should become necessary. We observed a complication that, to our knowledge, has not been reported previously. Five patients developed intermittent respiratory difficulties 2 to 21 days (mean, 8 days) after undergoing PDT. The cause turned out to be the periodic obstruction of the tracheal cannula by hematoma and the swelling of the posterior tracheal wall, which had been caused by intermittent pressure and chafing of the cannula on the tracheal wall. In between the episodes of obstruction, the cannula was open and functioning normally, which made the diagnosis difficult to establish. CONCLUSIONS: Bronchoscopy-assisted PDT is a safe and effective procedure when performed by a team of experienced physicians under controlled circumstances. The intermittent obstruction of the cannula caused by swelling and irritation of the posterior tracheal wall should be considered in patients who develop unexplained paroxysmal respiratory problems some time after undergoing PDT or ST.

Immunoparalysis as a cause for invasive aspergillosis?

Aspergillus infections are among the most feared opportunistic infections in humans. These organisms are ubiquitous in nature; protection against infection is usually provided by anatomical barriers and by the immune system. Tissue invasion by Aspergillus is uncommon, occurring primarily in the setting of immunosuppression. The prognosis of invasive aspergillosis is very poor. Although it is widely recognised that critically ill patients in the Intensive Care Unit (ICU) are at risk for nosocomial infections, it is not generally appreciated that such patients may also be at risk for opportunistic infections usually seen only in immunocompromised patients. This might be explained by a biphasic immunological pattern during sepsis: an early hyperinflammatory phase followed by an anti-inflammatory response, leading to a hypo-inflammatory state, the so-called compensatory anti-inflammatory response syndrome (CARS or immunoparalysis). We describe four patients admitted to our ICU for various reasons, without a history of abnormal immune function, who developed invasive pulmonary aspergillosis. We hypothesise that the occurrence of these opportunistic infections in our patients may have been due to immunoparalysis, and that perhaps all ICU patients with sepsis and multiple organ dysfunction syndrome (MODS) may be at risk for opportunistic infections such as aspergillosis as a result of this syndrome. Physicians treating critically ill patients in the ICU should be aware of the CARS/immunoparalysis syndrome and its potential to cause opportunistic infections, even in patients with normal immune function prior to ICU admission.

Relative adrenal insufficiency as a predictor of disease severity, mortality, and beneficial effects of corticosteroid treatment in septic shock.

OBJECTIVE: To evaluate the concept of relative adrenal insufficiency necessitating corticosteroid therapy in septic shock. DESIGN: Retrospective study. SETTING: Medical-surgical intensive care unit of a university hospital. PATIENTS: We studied 218 consecutive patients with septic shock in a 3-yr period who underwent a short 250-microg adrenocorticotropic hormone test because of >6 hrs of hypotension requiring repeated fluid challenges and/or vasopressor/inotropic treatment. INTERVENTIONS: The test was performed by intravenously injecting 250 mug of synthetic adrenocorticotropic hormone and measuring cortisol immediately before and 30 and 60 mins postinjection. MEASUREMENTS AND MAIN RESULTS: Intensive care unit mortality until day 28 was 22%. Nonsurvivors had greater disease severity, as exemplified by higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score, on the day of adrenocorticotropic hormone testing. Cortisol levels directly correlated with albumin levels. Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score increased with higher strata of baseline cortisol/albumin or lower cortisol increases/albumin ratios as measures of free cortisol. Baseline cortisol, cortisol increases, and albumin levels did not independently contribute to mortality prediction by disease severity and absence of corticosteroid (hydrocortisone) treatment in a Cox proportional hazard model, although adrenocorticotropic hormone-induced cortisol increase <100 nmol/L (n = 53) predicted mortality (p = .007). Posttest treatment by corticosteroids (n = 161, 74%) was associated with higher survival in patients with cortisol increase <100 nmol/L (p = .0296). CONCLUSIONS: In intensive care unit patients with septic shock, the cortisol response to adrenocorticotropic hormone inversely relates to disease severity, independent of blood cortisol binding. An adrenocorticotropic hormone-induced cortisol increase <100 nmol/L predicts mortality and beneficial effects of corticosteroid treatment. The data favor relative adrenal insufficiency.

Relative adrenal insufficiency: an identifiable entity in nonseptic critically ill patients?

OBJECTIVE: To determine whether relative adrenal insufficiency (RAI) can be identified in nonseptic hypotensive patients in the intensive care unit (ICU). DESIGN: Retrospective study in a medical-surgical ICU of a university hospital. PATIENTS: One hundred and seventy-two nonseptic ICU patients (51% after trauma or surgery), who underwent a short 250 microg ACTH test because of > 6 h hypotension or vasopressor/inotropic therapy. MEASUREMENTS: On the test day, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score were calculated to estimate disease severity. The ICU mortality until day 28 was recorded. Best discriminative levels of baseline cortisol, increases and peaks were established using receiver operating characteristic curves. These and corticosteroid treatment (in n = 112, 65%), among other variables, were examined by multiple logistic regression and Cox proportional hazard regression analyses to find independent predictors of ICU mortality until day 28. RESULTS: ICU mortality until day 28 was 23%. Nonsurvivors had higher SAPS II and SOFA scores. Baseline cortisol levels correlated directly with albumin levels and SAPS II. In the multivariate analyses, a cortisol baseline > 475 nmol/l and cortisol increase < 200 nmol/l predicted mortality, largely dependent on disease severity but independent of albumin levels. Corticosteroid (hydrocortisone) treatment was not associated with an improved outcome, regardless of the ACTH test results. CONCLUSION: In nonseptic hypotensive ICU patients, a low cortisol/ACTH response and treatment with corticosteroids do not contribute to mortality prediction by severity of disease. The data thus argue against RAI identifiable by cortisol/ACTH testing and necessitating corticosteroid substitution treatment in these patients.